The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs

Abstract

Background: In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study.

Results: Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 ± 11/7 and 74/3 ± 17/5 mmHg, respectively, with associated native heart rates of 80 ± 7 and 96 ± 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation.

Conclusions: We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens.

Keywords: Cardiac anatomy; Cardiac physiology; Heart-lung bloc; Reanimation.

Fig. 1

(Top right) External view of human heart 277 in systole and attached to the system. (Center) Flow diagram for a functional heart and lung reanimation consisting of: (1) a respirator connected to the cannulated trachea and thus attached to the lung(s), (2) a pre-load chamber for the right side of the heart, (3) an aortic after-load chamber which mimics the resistance that the left ventricle works against, (4) a left pre-load chamber employed when only one lung is present, (5) an oxygenator reservoir for pooling fluid expelled by any cannulated branch of the pulmonary artery, (6 & 7) fluid pumps to maintain the pre-load pressures, (8) hemostasis valves that allow access for delivery of cameras, instruments, and assorted devices, (9) valves that may also be used to redirect flow as physiologically appropriate, while (10) cannulation of the pulmonary vein(s) are shown here for a right lung preparation, but are absent or translated when either both lungs or the left alone respectively are used

Fig. 2

Image series obtained from reanimated human heart-lung bloc 284 (a, b) and 277 (c, d). The image series shows the path through the distal pulmonary arteries (a, b) and veins (c, d). The corresponding fluoroscopic images (b, d) in each case show the relative locations of the videoscopes (a, c). A video of the journey through the vasculature can be viewed as well (see Additional file 1)

Fig. 3

Time series of images from human heart 277. This series shows tricuspid valve closure from the right ventricle (a) and right atria (b) through slightly greater than one cardiac cycle. In series B, the septal leaflet can be seen toward the bottom left of the images. Images are displayed 1/15th per second apart in time. Panel C displays ice formation on the distal portion of a cryoballoon ablation catheter (Artic Front, Medtronic PLC, Minneapolis, MN, USA) as seen from within the pulmonary vein. The images are spaced 20 s, 1, 2, and 3 min from the start of ablation cooling